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Status |
Public on Sep 30, 2019 |
Title |
Tumour Cell Heterogeneity Instructs Fibroblast Diversity and Reciprocal Signalling [dataset 2] |
Organism |
Mus musculus |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
We investigated changes to murine pancreatic fibroblast gene expression in response to co-culture with 8 murine pancreatic tumour cell sub-populations. Tumours are complex ecosystems where phenotypically diverse tumour cells are embedded in a heterocellular environment. Using an in vitro model of intra-tumoral heterogeneity, we show that clonal tumour cell populations establish distinct interactions with stromal fibroblasts to expand phenotypic diversity across tumour and stromal cell populations. Heterocellular interactions drive differential engagement of tumour cell reciprocal signalling pathways, resulting in normalisation of cell-autonomous differences in MAPK signalling but diversification of AKT signalling. Consequently, tumour cell clones display differential cell-autonomous and non-cell autonomous dependencies. These results demonstrate that tumour-stroma interactions amplify tumour cell autonomous diversity and that our existing perspective on tumour cell heterogeneity underestimates functional diversity.
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Overall design |
RNA sequencing of fibroblasts after direct co-culture with tumour sub-clones
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Contributor(s) |
McCarthy A, Jorgensen C |
Citation(s) |
36411320 |
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Submission date |
Aug 06, 2019 |
Last update date |
Dec 15, 2022 |
Contact name |
Claus Jorgensen |
E-mail(s) |
claus.jorgensen@cruk.manchester.ac.uk
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Organization name |
Cancer Research UK Manchester Institute
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Lab |
Systems Oncology
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Street address |
Alderley Park
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City |
Macclesfield |
State/province |
Lancs |
ZIP/Postal code |
SK10 4TG |
Country |
United Kingdom |
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Platforms (1) |
GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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Samples (36)
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This SubSeries is part of SuperSeries: |
GSE135436 |
Tumour Cell Heterogeneity Instructs Fibroblast Diversity and Reciprocal Signalling |
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Relations |
BioProject |
PRJNA558891 |
SRA |
SRP217526 |